Chronic low-grade inflammation is causally linked to the pathogenesis of obesity-associated metabolic diseases, such as insulin resistance (IR), type 2 diabetes, cardiovascular disease and non-alcoholic fatty liver disease. Fat overload in the adipocyte triggers circulating monocyte recruitment into lipid-laden adipose tissue, which produces a large quantity of pro-inflammatory mediators. This perturbs insulin signaling in adipose tissue, eventually inducing systemic inflammation and IR. As such, both metabolic and inflammatory components largely contribute to the development of chronic low-grade inflammation in obesity. Complementary and alternative medicine (CAM) natural products that can effectively combat chronic inflammation with minimal adverse side-effects are much needed. Spirulina platensis (SP) is a blue-green alga (BGA) that has proven to be safe for human consumption. During the past several years, we have investigated anti-inflammatory properties of BGA extracts, and more specifically a SP organic extract (SPE) using both in vitro and in vivo models and have found substantial evidence for their potential in the prevention of obesity-induced inflammation. However, major gaps exist in our knowledge regarding the bioactive components from edible BGA, which hinders the standardization and broader utilization of these CAM natural products. Very little is known about the chemical composition of BGA. Currently, standardization utilizes -carotene, total carotenoids, and/or phycocyanin content for quality assurance. These components have not been shown to cause the potent anti-inflammatory activity of BGA and thus are not appropriate marker compounds for chemical standardization based on biological activity. The following specific aims are thus proposed: SA1, isolation and identification of anti-inflammatory compounds from SP extracts; and SA2, identification of molecular mechanisms responsible for anti-inflammatory effects of SP extracts and purified compounds. The identification of bioactive metabolites responsible for the anti-inflammatory effects of BGA will help to support future standardization of these CAM products and additional information regarding their mechanism of action will allow for further preclinical and clinical development.